This Mental Retardation Research Center (MRRC), established in 1990, is a collaboration between three affiliated institutions that share one campus: the Children's Hospital of Philadelphia, the University of Pennsylvania and Children's Seashore House. In this first competitive renewal, funds are requested to provide support to six core units and a new program development project. The units include: Administrative Core: This core will continue to support the general management of center associates. It will also serve as the editorial office of the new MRRC sponsored journal, Mental Retardation and Developmental Disabilities Research Reviews. Study Design and Statistical Analysis Core: this core continues to provide consultation on study design, data management and statistical analysis. A new function will be assistance in the incorporation of biomedical ethics in study design. Molecular Genetics Core: this core continues to provide a centralized nucleic acid-protein research facility as well as cytogenetic karyotyping. It has been expanded to include fluorescent based PCR, mutation detection with cosmid contigs, and screening of YAC libraries. Analytical Neurochemistry and Spectroscopy Core (previously entitled Neuroscience core): this core provides neurochemistry services, gas chromatography-mass spectrometry and a new service, in vivo magnetic resonance spectroscopy. Cellular Neuroscience Core (previously entitled Neuropathology core): this core continues to provide neuronal cell cultures, light microscopy, and cytoarchitectural analysis; a new function, confocal microscopy, has been added. Functional Neuroimaging Core: this reconceived core will provide functional magnetic resonance imaging, PET scanning, compliance training and cortical activation tasks. We have also proposed to develop a New Program Development Project to fund young investigators entering the field of MRDD. After a University wide search, David Lynch, M.D., Ph.D., a neurologist was chosen to pursue a new molecular biology project concerning the chemical definition and pharmacological characterization of the N-methyl-D-aspartate glutamate receptor during central nervous system development. Overall, the core units will provide services to 45 NIH research projects with funding of more than $7 million/year, over $1 million from NICHD. A total of 56 University faculty members will be affiliated with the MRRC as Center Associates or Center Staff. These faculty represent 15 departments from 6 major components at the University of Pennsylvania (The School of Medicine, College of Arts and Sciences, Veterinary School, Wistar Institute, Children's Hospital of Philadelphia and Children's Seashore House). With the continued support of the MRRC, we expect to further enhance research productivity in the area of mental retardation and developmental disabilities.